• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Deletion of Mecp2 in Sim1-expressing neurons reveals a critical role for MeCP2 in feeding behavior, aggression, and the response to stress.

Rett Syndrome (RTT) is an autism spectrum disorder caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2). In order to map the neuroanatomic origins of the complex neuropsychiatric behaviors observed in patients with RTT and to uncover endogenous functions of MeCP2 in the hypothalamus, we removed Mecp2 from Sim1-expressing neurons in the hypothalamus using Cre-loxP technology. Loss of MeCP2 in Sim1-expressing neurons resulted in mice that recapitulated the abnormal physiological stress response that is seen upon MeCP2 dysfunction in the entire brain. Surprisingly, we also uncovered a role for MeCP2 in the regulation of social and feeding behaviors since the Mecp2 conditional knockout (CKO) mice were aggressive, hyperphagic, and obese. This study demonstrates that deleting Mecp2 in a defined brain region is an excellent approach to map the neuronal origins of complex behaviors and provides new insight about the function of MeCP2 in specific neurons.

Pubmed ID: 18817733

Authors

  • Fyffe SL
  • Neul JL
  • Samaco RC
  • Chao HT
  • Ben-Shachar S
  • Moretti P
  • McGill BE
  • Goulding EH
  • Sullivan E
  • Tecott LH
  • Zoghbi HY

Journal

Neuron

Publication Data

September 25, 2008

Associated Grants

  • Agency: Autism Speaks, Id: AS1622
  • Agency: NICHD NIH HHS, Id: HD024064
  • Agency: NINDS NIH HHS, Id: K08 NS052240
  • Agency: NINDS NIH HHS, Id: K08 NS052240-01
  • Agency: NINDS NIH HHS, Id: K08 NS052240-02
  • Agency: NINDS NIH HHS, Id: K08 NS052240-03
  • Agency: NINDS NIH HHS, Id: K08 NS052240-04
  • Agency: NINDS NIH HHS, Id: K08 NS052240-05
  • Agency: NINDS NIH HHS, Id: NS057819
  • Agency: NICHD NIH HHS, Id: P30 HD024064
  • Agency: NICHD NIH HHS, Id: P30 HD024064-20
  • Agency: NINDS NIH HHS, Id: R01 NS057819
  • Agency: NINDS NIH HHS, Id: R01 NS057819-03
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Adaptation, Psychological
  • Adiposity
  • Aggression
  • Animals
  • Appetite Regulation
  • Basic Helix-Loop-Helix Transcription Factors
  • Feeding Behavior
  • Gene Deletion
  • Genetic Engineering
  • Hypothalamus
  • Methyl-CpG-Binding Protein 2
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Neurons
  • Repressor Proteins
  • Social Behavior
  • Stress, Psychological